Utility of Plasma Metanephrines in Adrenal Venous Sampling in Primary Aldosteronism

Abstract

Introduction: Adrenal Venous Sampling (AVS) is the most reliable means of identifying surgically curable subtypes of primary aldosteronism (PA). Cortisol levels are used to determine cannulation success and lateralization. However, cortisol has a variable secretion pattern and long-half life, and can be co-secreted by adrenal adenomas, leading to misinterpretation of results. Plasma metanephrines (MN) are a possible alternative analyte. MN levels are unaffected by stress, have a short half-life of 3–6 minutes and are released continuously by the adrenals, resulting in very high concentration gradients between the adrenal veins (AV) and peripheral veins (PV), thus providing a sensitive means to determine cannulation success. Premise:The objective of this study was to see if MN can be used in lieu of cortisol in AVS. A secondary end-point was to see if the data was particularly useful in patients who are known co-secretors of cortisol. Methods: Data from AVS carried out without cosyntropin stimulation, from October 2018 to March 2020, were analysed retrospectively. Of these, 51 had additional samples drawn for MN at the time of the procedure and were recruited. Six patients were identified as having autonomous cortisol secretion as they failed an overnight dexamethasone suppression test (ONDST). The data was analysed using cortisol and MN separately and then compared with regards to their selectivity and lateralization index. Data was also analysed to see if known co-secretors had an elevated cortisol/MN ratio of more than 2 on the affected side as described in previous papers. Results: When compared to cannulation and lateralization outcomes using cortisol, similar results were obtained using, a MN AV/PV ratio of more than 12 to indicate successful cannulation and an aldosterone/MN ratios of greater than 5 to confirm lateralization. Contralateral suppression to less than 0.5 for aldosterone/MN below the PV was seen in unilateral disease. With regards to the six co-secretors, all had elevated cortisol/MN ratios of more than 2 on the affected side. Three had concordant results but the other three had discrepant results, with MN analysis suggesting unilateral disease and cortisol measurements suggesting bilateral disease. Two had undergone surgery with biopsy confirming unilateral disease that correlated with MN analysis. The third is under medical management. Conclusion: This is the first study evaluating the use of MN to determine lateralisation of aldosterone production in PA. Further studies are needed, but using MN may be a more reliable alternative to cortisol in the analysis of AVS before definitive surgery in particular in patients with cortisol co-secretion.